PROJECT SUMMARY/ABSTRACT Sleep disturbance negatively impacts many biological systems and may be detrimental to skeletal health. Bone remodeling, which is important for bone mass and strength, increases overnight, a time when millions experience disrupted sleep. Epidemiological data and animal studies suggest a link between sleep disturbance and bone but the direction and the mechanisms by which sleep affects bone are not fully understood. The overall objective of this project is to establish and quantify the skeletal effects of disrupted sleep and to investigate the mechanisms by which bone remodeling and sleep are linked. The central hypothesis is that sleep disturbance (e.g., sleep loss, circadian shifts) negatively impacts bone health by altering the balance between bone resorption and bone formation, and is particularly detrimental during skeletally vulnerable periods such as during and after the menopausal transition. The specific aims are: 1. Examine the physiological mechanisms that control rhythms in bone remodeling and investigate how circadian shifts and accumulating sleep loss affect bone turnover in otherwise healthy men. This aim will use samples from a previously performed clinical experiment that manipulated sleep-wake cycles. 2. Determine the association between sleep loss and bone turnover and bone mineral density in older men and peri- and post-menopausal women using cross-sectional analyses of observational cohort studies. This represents a novel inquiry into these cohorts to confirm the association between sleep and bone while exploring differences related to sex and sex hormone status. 3. Evaluate mechanisms by which sleep loss alters the balance in bone remodeling through a small, clinical intervention study. These preliminary data will support the development of an R01 grant application. This research fills a knowledge gap in the fields of sleep and bone research that could impact the clinical evaluation and treatment of osteoporosis. If the hypothesis is shown to be true, sleep disruption could be a novel, modifiable risk factor for osteoporosis. The candidate, Christine Swanson, M.D., is an outstanding junior investigator with an exceptional background including Endocrinology clinical & research training (specializing in bone) at OHSU and the completion of a Masters of Clinical Research during the K23 award period. Through mentorship from Drs. Wendy Kohrt and Kenneth Wright, coursework, and the successful completion of the project?s specific aims, the candidate will develop a knowledge base and skillset in bone and sleep research that will set her on the path to achieve her overall goal of becoming a successful independent physician scientist.